Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

Ajogbasile, Fehintola V.; Oluniyi, Paul E.; Kayode, Adeyemi T.; Akano, Kazeem; Adegboyega, Benjamin B; Philip, Courage; Ogbulafor, Nnenna; Okafor, Henrietta U.; Oguche, Stephen; Wammanda, Robinson D.; Mokuolu, Olugbenga A.; Folarin, Onikepe A.; Happi, Christian T.

doi:10.1371/journal.pone.0264548

Cited by 14 publications

(10 citation statements)

References 45 publications

(51 reference statements)

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“…The all 3 Q613H were detected in the migrant workers from Nigeria, which was similar as reported before [31]. C469C, a common synonymous mutant allele of pfK13 found in African isolates, the proportion in our study was similar as that in Burkina Faso and Senegal [32][33][34]. The pfK13 mutation allele S549S, to our knowledge, was rstly identi ed in the migrant workers from Guinea, Equatorial Guinea, and The Democratic Republic of the Congo (Congo DRC).…”

Section: Discussionsupporting

confidence: 88%

Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

Kong

Feng

et al. 2022

Preprint

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Background The artemisinin-based combination therapies (ACTs) was recommended as the first line drugs by the World Health Organization to treat uncomplicated Plasmodium falciparum. However, the emergence and spread of P. falciparum resistant to artemisinins and their partner drugs is a significant risk for the global effort to reduce disease burden facing the world. Method A retrospective study was conducted to explore the prevalence and spatial distribution of pfK13 and pfcrt polymorphisms among imported P. falciparum isolates in years 2015–2019 in Shandong Province in eastern China. Individual epidemiological information was collected from a web-based reporting system were reviewed and analysed. Results A total of 425 P. falciparum blood samples in 2015–2019 were included and we found that 7.3% (31/425) carried pfK13 mutations. Out of the isolates that carried K13 mutations, 54.8% (17/31) were nonsynonymous polymorphisms. The mutant allele A578S, Q613H, C469C, and S549S in pfK13 were the more frequently detected allele, the mutation rate was the same as 0.7% (3/425). Another allele pfK13C580Y, closely associated with artemisinin (ART) resistance, was found as 0.5% (2/425), which was found in Cambodia. About 45.2% (14/31) of the P. falciparum isolates had pfK13 mutations resembled those from Western Africa. For the pfcrt gene, T76T356 and T76 were more frequent in all 13 different haplotypes with 4.7% (20/425) and 4.2% (18/425) that identified in 77 isolates (18.1%, 77/425). The CVIET and CVIKT mutant at loci 72–76 have exhibited a prevalence of 3.5% and 0.7%, respectively. The CVIET were mainly distributed in Congo (5.2%, 4/77) and Mozambique (5.2%, 4/77). No mutations were found at loci 97, 101 and 145. For polymorphisms at locus 356, a total of 24 isolates were identified and mainly from Congo (29.2%, 7/24). Conclusion These findings indicate a low prevalence of pfK13 in the African isolates, while the mutations related to piperaquine (PPQ) resistance remain at a certain level. Therefore, continuous molecular surveillance of pfcrt mutations and in vitro susceptibility tests related to PPQ are necessary.

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Section: Discussionsupporting

confidence: 88%

Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

Kong

Feng

et al. 2022

Preprint

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“…The all 3 Q613H were detected in the migrant workers from Nigeria, which was similar as reported before [ 34 ]. The synonymous mutant allele C469C, which was common in Africa, was identified in this study and the proportion was similar as reported in Burkina Faso and Senegal [ 35 – 37 ]. The Pfk13 mutant allele S549S, to our knowledge, was firstly identified in the migrant workers from Guinea, Equatorial Guinea, and Congo DRC.…”

Section: Discussionsupporting

confidence: 88%

Molecular surveillance of artemisinin resistance-related Pfk13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015 to 2019

Kong

Feng

et al. 2022

Malar J

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Background Artemisinin-based combination therapy (ACT) has been recommended as the first-line treatment by the World Health Organization to treat uncomplicated Plasmodium falciparum malaria. However, the emergence and spread of P. falciparum resistant to artemisinins and their partner drugs is a significant risk for the global effort to reduce disease burden facing the world. Currently, dihydroartemisinin-piperaquine (DHA-PPQ) is the most common drug used to treat P. falciparum, but little evidence about the resistance status targeting DHA (ACT drug) and its partner drug (PPQ) has been reported in Shandong Province, China. Methods A retrospective study was conducted to explore the prevalence and spatial distribution of Pfk13 and Pfcrt polymorphisms (sites of 72–76, and 93–356) among imported P. falciparum isolates between years 2015–2019 in Shandong Province in eastern China. Individual epidemiological information was collected from a web-based reporting system were reviewed and analysed. Results A total of 425 P. falciparum blood samples in 2015–2019 were included and 7.3% (31/425) carried Pfk13 mutations. Out of the isolates that carried Pfk13 mutations, 54.8% (17/31) were nonsynonymous polymorphisms. The mutant alleles A578S, Q613H, C469C, and S549S in Pfk13 were the more frequently detected allele, the mutation rate was the same as 9.7% (3/31). Another allele Pfk13 C580Y, closely associated with artemisinin (ART) resistance, was found as 3.2% (2/31), which was found in Cambodia. A total of 14 mutant isolates were identified in Western Africa countries (45.2%, 14/31). For the Pfcrt gene, the mutation rate was 18.1% (77/425). T76T356 and T76 were more frequent in all 13 different haplotypes with 26.0% (20/77) and 23.4% (18/77). The CVIET and CVIKT mutant at loci 72–76 have exhibited a prevalence of 19.5% (15/77) and 3.9% (3/77), respectively. The CVIET was mainly observed in samples from Congo (26.7%, 4/15) and Mozambique (26.7%, 4/15). No mutations were found at loci 97, 101 and 145. For polymorphisms at locus 356, a total of 24 isolates were identified and mainly from Congo (29.2%, 7/24). Conclusion These findings indicate a low prevalence of Pfk13 in the African isolates. However, the emergence and increase in the new alleles Pfcrt I356T, reveals a potential risk of drug pressure in PPQ among migrant workers returned from Africa. Therefore, continuous molecular surveillance of Pfcrt mutations and in vitro susceptibility tests related to PPQ are necessary.

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“…No mutations in kelch13 were identified that have previously been associated with artemisinin resistance. Five kelch13 mutations were identified, three synonymous changes (A627A and S649S (both in Navrongo), and a sample from Accra with C469C), and two non-synonymous mutations: Q613H (in Accra) and N629Y (in Navrongo), which have previously been reported in West Africa [78,79] and are not considered to be associated with artemisinin resistance ( Supplementary Notes ).…”

Section: Resultsmentioning

confidence: 98%

“…Q613H (in Accra) and N629Y (in Navrongo), which have previously been reported in West Africa [78,79] and are not considered to be associated with artemisinin resistance (Supplementary Notes).…”

Section: Drug Resistance Marker Frequenciesmentioning

confidence: 84%

Nanopore sequencing for real-time genomic surveillance ofPlasmodium falciparum

Girgis

Adika

Nenyewodey

et al. 2022

Preprint

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Malaria is a global public health priority causing over 600,000 deaths annually, mostly young children living in Sub-Saharan Africa. Molecular surveillance can provide key information for malaria control, such as the prevalence and distribution of antimalarial drug resistance. However, genome sequencing capacity in endemic countries can be limited. Here, we have implemented an end-to-end workflow for Plasmodium falciparum genomic surveillance in Ghana using Oxford Nanopore Technologies, targeting antimalarial resistance markers and the leading vaccine antigen circumsporozoite protein (csp). The workflow was rapid, robust, accurate, affordable and straightforward to implement. We found that P. falciparum parasites in Ghana had become largely susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine (SP) resistance, and no evidence of artemisinin resistance. Multiple Single Nucleotide Polymorphism (SNP) differences from the vaccine csp sequence were identified, though their significance is uncertain. This study demonstrates the potential utility and feasibility of malaria genomic surveillance in endemic settings using Nanopore sequencing.

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Molecular profiling of the artemisinin resistance Kelch 13 gene in Plasmodium falciparum from Nigeria

Cited by 14 publications

References 45 publications

Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

Molecular surveillance of artemisinin resistance-related pfK13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015–2019

Molecular surveillance of artemisinin resistance-related Pfk13 and pfcrt polymorphisms in imported Plasmodium falciparum isolates reported in eastern China from 2015 to 2019

Nanopore sequencing for real-time genomic surveillance ofPlasmodium falciparum

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